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排序方式: 共有698条查询结果,搜索用时 15 毫秒
21.
Spread of X inactivation on chromosome 15 is associated with a more severe phenotype in a girl with an unbalanced t(X; 15) translocation 下载免费PDF全文
22.
B-cell growth factor receptor expression and B-cell growth factor response of leukemic B cell precursors and B lineage lymphoid progenitor cells 总被引:8,自引:1,他引:8
Uckun FM; Fauci AS; Heerema NA; Song CW; Mehta SR; Gajl-Peczalska K; Chandan M; Ambrus JL 《Blood》1987,70(4):1020-1034
The purpose of this study was to analyze the expression of B cell growth factor (BCGF) receptors and to elucidate the biologic effects of biochemically purified natural BCGF at the B cell precursor stage of human B lineage lymphoid differentiation. The specific binding of radioiodinated high-mol-wt BCGF (125I-HMW-BCGF) and low-molecular-wt BCGF (125I-LMW-BCGF) to fresh marrow blasts from B cell precursor acute lymphoblastic leukemia (ALL) patients was initially investigated. The estimated number of radioiodinated BCGF molecules bound per blast ranged from undetectable to 24.3 X 10(3) for HMW-BCGF, and from 11.5 X 10(3) to 457.8 X 10(3) for LMW-BCGF. In 3H-TdR incorporation assays, 75% of cases showed a significant response to LMW-BCGF with a median stimulation index of 9.3. By comparison, only 33% of cases showed a significant response to HMW-BCGF with a median stimulation index of 2.4. Subsequently, B cell precursor colony assays were performed to assess and compare the biologic effects of BCGF on leukemic B lineage lymphoid progenitor cells. Among 28 cases studied, 57% responded to both HMW-BCGF and LMW-BCGF, 21% responded only to LMW-BCGF, and the remaining cases showed no proliferative response to either growth factor. The response patterns of virtually pure populations of FACS- sorted leukemic B cell precursors were essentially identical to the proliferative responses of unsorted leukemic B-cell precursors. Synergistic effects between HMW-BCGF and LMW-BCGF were observed in 80% of the cases that responded to both. The numbers of cell-bound radioiodinated BCGF molecules, the stimulation indices, as well as the number of B cell precursor colonies in BCGF-stimulated cultures showed a marked interpatient variation. Patients with structural chromosomal abnormalities (SCAs) involving 12p11-13 or patients with a Philadelphia chromosome showed a greater HMW-BCGF response at the level of leukemic progenitor cells than did other patients (P = .02). The LMW-BCGF response was significantly greater for patients with SCA than for patients without SCA (P = .04). The response of leukemic progenitor cells to HMW-BCGF or LMW-BCGF did not correlate with sex, age, disease status, FAB morphology, WBC at diagnosis, or immunophenotype. To our knowledge, this study represents the first detailed analyses of BCGF receptor expression and BCGF effects in B cell precursor ALL. The data presented provide direct evidence for the expression of functional receptors for both HMW-BCGF and LMW-BCGF in B cell precursor ALL. 相似文献
23.
The use of 7-amino actinomycin D in identifying apoptosis: simplicity of use and broad spectrum of application compared with other techniques 总被引:9,自引:5,他引:9
Philpott NJ; Turner AJ; Scopes J; Westby M; Marsh JC; Gordon-Smith EC; Dalgleish AG; Gibson FM 《Blood》1996,87(6):2244-2251
The detection and quantitation of apoptotic cells is becoming increasingly important in the investigation of the role of apoptosis in cellular proliferation and differentiation. The pathogenesis of hematologic disorders such as aplastic anemia and the development of neoplasia are believed to involve dysregulation of apoptosis. To quantitate accurately the proportion of apoptosis cells within different cell types of a heterogeneous cell population such as blood or bone marrow, a method is required that combines the analysis of large numbers of cells with concurrent immunophenotyping of cell surface antigens. In this study, we have evaluated such a method using the fluorescent DNA binding agent, 7-amino actinomycin D (7AAD), to stain three diverse human cell lines, induced to undergo apoptosis by three different stimuli. Flow cytometric analysis defines three populations on the basis of 7AAD fluorescence and forward light scatter. We have shown by cell sorting and subsequent morphological assessment and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling that the populations defined by 7AAD represent live, apoptotic, and late-apoptotic/dead cells. This method is quick, simple, reproducible, and cheap and will be a valuable tool in the investigation of the role of apoptosis in normal physiology and in disease states. 相似文献
24.
Duncan WC; Illingworth PJ; Young FM; Fraser HM 《Human reproduction (Oxford, England)》1998,13(9):2532-2540
The molecular mechanisms involved in luteolysis are still unclear in the
primate. This study aimed to investigate the effect of induced luteolysis
on the ovarian luteinizing hormone (LH) receptor and the steroidogenic
enzyme, 3beta-hydroxysteroid dehydrogenase (3beta-HSD) in the marmoset
monkey. Luteolysis was induced in the mid-luteal phase either directly by
systemic prostaglandin F2alpha (PGF2alpha), or indirectly by LH withdrawal
using systemic gonadotrophin releasing hormone antagonist (GnRHant)
treatment. The LH receptor was studied by isotopic mRNA in-situ
hybridization and in-situ ligand binding and 3beta-HSD expression was
studied using isotopic mRNA in-situ hybridization and immunohistochemistry.
Induced luteolysis was associated with a reduction in the expression of LH
receptor (P < 0.0001) and 3beta-HSD mRNA, closely followed by a
reduction in the LH receptor (P < 0.05) and 3beta-HSD protein
concentrations within 24 h. There were no differences in the findings
whether luteolysis was induced with PGF2alpha or GnRHant. This study shows
that disparate mechanisms to induce luteolysis in the primate result in an
identical rapid loss of the LH receptor and 3beta-HSD. In conclusion,
induced luteolysis leads to rapid loss of the steroidogenic pathway in
luteal cells.
相似文献
25.
da Silva Xavier G Farhan H Kim H Caxaria S Johnson P Hughes S Bugliani M Marselli L Marchetti P Birzele F Sun G Scharfmann R Rutter J Siniakowicz K Weir G Parker H Reimann F Gribble FM Rutter GA 《Diabetologia》2011,54(4):819-827
Aims/hypothesis
We assessed whether per-arnt-sim (PAS) domain-containing protein kinase (PASK) is involved in the regulation of glucagon secretion.Methods
mRNA levels were measured in islets by quantitative PCR and in pancreatic beta cells obtained by laser capture microdissection. Glucose tolerance, plasma hormone levels and islet hormone secretion were analysed in C57BL/6 Pask homozygote knockout mice (Pask ?/?) and control littermates. Alpha-TC1-9 cells, human islets or cultured E13.5 rat pancreatic epithelia were transduced with anti-Pask or control small interfering RNAs, or with adenoviruses encoding enhanced green fluorescent protein or PASK.Results
PASK expression was significantly lower in islets from human type 2 diabetic than control participants. PASK mRNA was present in alpha and beta cells from mouse islets. In Pask ?/? mice, fasted blood glucose and plasma glucagon levels were 25?±?5% and 50?±?8% (mean ± SE) higher, respectively, than in control mice. At inhibitory glucose concentrations (10?mmol/l), islets from Pask ?/? mice secreted 2.04?±?0.2-fold (p?0.01) more glucagon and 2.63?±?0.3-fold (p?0.01) less insulin than wild-type islets. Glucose failed to inhibit glucagon secretion from PASK-depleted alpha-TC1-9 cells, whereas PASK overexpression inhibited glucagon secretion from these cells and human islets. Extracellular insulin (20?nmol/l) inhibited glucagon secretion from control and PASK-deficient alpha-TC1-9 cells. PASK-depleted alpha-TC1-9 cells and pancreatic embryonic explants displayed increased expression of the preproglucagon (Gcg) and AMP-activated protein kinase (AMPK)-alpha2 (Prkaa2) genes, implying a possible role for AMPK-alpha2 downstream of PASK in the control of glucagon gene expression and release.Conclusions/interpretation
PASK is involved in the regulation of glucagon secretion by glucose and may be a useful target for the treatment of type 2 diabetes. 相似文献26.
Gloyn AL Reimann F Girard C Edghill EL Proks P Pearson ER Temple IK Mackay DJ Shield JP Freedenberg D Noyes K Ellard S Ashcroft FM Gribble FM Hattersley AT 《Human molecular genetics》2005,14(7):925-934
Neonatal diabetes can either remit and hence be transient or else may be permanent. These two phenotypes were considered to be genetically distinct. Abnormalities of 6q24 are the commonest cause of transient neonatal diabetes (TNDM). Mutations in KCNJ11, which encodes Kir6.2, the pore-forming subunit of the ATP-sensitive potassium channel (K(ATP)), are the commonest cause of permanent neonatal diabetes (PNDM). In addition to diabetes, some KCNJ11 mutations also result in marked developmental delay and epilepsy. These mutations are more severe on functional characterization. We investigated whether mutations in KCNJ11 could also give rise to TNDM. We identified the three novel heterozygous mutations (G53S, G53R, I182V) in three of 11 probands with clinically defined TNDM, who did not have chromosome 6q24 abnormalities. The mutations co-segregated with diabetes within families and were not found in 100 controls. All probands had insulin-treated diabetes diagnosed in the first 4 months and went into remission by 7-14 months. Functional characterization of the TNDM associated mutations was performed by expressing the mutated Kir6.2 with SUR1 in Xenopus laevis oocytes. All three heterozygous mutations resulted in a reduction in the sensitivity to ATP when compared with wild-type (IC(50) approximately 30 versus approximately 7 microM, P-value for is all <0.01); however, this was less profoundly reduced than with the PNDM associated mutations. In conclusion, mutations in KCNJ11 are the first genetic cause for remitting as well as permanent diabetes. This suggests that a fixed ion channel abnormality can result in a fluctuating glycaemic phenotype. The multiple phenotypes associated with activating KCNJ11 mutations may reflect their severity in vitro. 相似文献
27.
28.
29.
Human Y chromosome azoospermia factors (AZF) mapped to different subregions in Yq11 总被引:56,自引:0,他引:56
Vogt PH; Edelmann A; Kirsch S; Henegariu O; Hirschmann P; Kiesewetter F; Kohn FM; Schill WB; Farah S; Ramos C; Hartmann M; Hartschuh W; Meschede D; Behre HM; Castel A; Nieschlag E; Weidner W; Grone HJ; Jung A; Engel W; Haidl G 《Human molecular genetics》1996,5(7):933-943
In a large collaborative screening project, 370 men with idiopathic
azoospermia or severe oligozoospermia were analysed for deletions of 76 DNA
loci in Yq11. In 12 individuals, we observed de novo microdeletions
involving several DNA loci, while an additional patient had an inherited
deletion. They were mapped to three different subregions in Yq11. One
subregion coincides to the AZF region defined recently in distal Yq11. The
second and third subregion were mapped proximal to it, in proximal and
middle Yq11, respectively. The different deletions observed were not
overlapping but the extension of the deleted Y DNA in each subregion was
similar in each patient analysed. In testis tissue sections, disruption of
spermatogenesis was shown to be at the same phase when the microdeletion
occurred in the same Yq11 subregion but at a different phase when the
microdeletion occurred in a different Yq11 subregion. Therefore, we propose
the presence of not one but three spermatogenesis loci in Yq11 and that
each locus is active during a different phase of male germ cell
development. As the most severe phenotype after deletion of each locus is
azoospermia, we designated them as: AZFa, AZFb and AZFc. Their probable
phase of function in human spermatogenesis and candidate genes involved
will be discussed.
相似文献
30.